Stromal Cells in Phyllodes Tumors of Breast Exhibit Stem Cell Marker Expression
Yanhong Zhang, Eugene Chung, Kathy A Toy, Lori J Pierce, Celina G Kleer. UC Davis Medical Center, Sacramento, CA; University of Michigan, Ann Arbor, MI
Background: Phyllodes tumors (PT) of breast are fibroepithelial neoplasms with stromal hypercelullarity, which is the basis for the diagnosis of benign, borderline and malignant. The histologic diagnosis of PT is often difficult, and the pathological features may not always predict clinical behavior. Previous studies suggest that EZH2 epigenetically regulates cell-type identity and cellular differentiation. We hypothesized that in PT, EZH2 and the stem cell marker ALDH1 may be expressed in stromal cells and associated with their degree of differentiation.
Design: Fourty-one PTs were histologically classified following WHO criteria, and blinded to outcome. Immunohistochemistry for EZH2 and ALDH1 was routinely performed on formalin-fixed, paraffin-embedded whole tissue sections. The percentage of ALDH1 expressing stromal and epithelial cells was recorded. A low or high EZH2 expression was identified based on a cutoff of 10% positive staining cells.
Results: Of the 41 PTs, 25 (61%) were benign, 8 (19.5%) borderline, and 8 (19.5%) malignant. EZH2 expression was low and rare in the epithelial cells, but significantly overexpressed in the stromal cells of borderline and malignant PT (4 of 8, 50% of each, p<0.005). ALDH1 was exclusively expressed in the stromal cells of PT, and significantly associated with the histological classification. ALDH1 positive cells were present in 40% of benign PT, 75% of borderline and 75% of malignant PT respectively (p<0.005).
Conclusions: EZH2 expression in PT may be helpful to distinguish benign from borderline and malignant tumors in challenging cases. Our data suggest that the stromal cells in PT exhibit a mesenchymal stem cell component, which increases with the degree of malignancy.
Monday, March 4, 2013 1:00 PM
Poster Session II # 49, Monday Afternoon